Abstract: Objective To investigate the effects of Shenxiong Pill on the infarct volume and expression of NF-κB in brains of rats with middle cerebral artery occlusion. Methods 169 SD rats were randomly divided into five groups: normal group, sham group, model group, cyclophosphamide group and Shenxiong Pill group. MCAO rat models were established by string ligation (for model, cyclophosphamide-treated and Shenxiong-treated groups). Rats in the Shenxiong Pill group was further randomly divided into sub-groups, receiving a range of high dose treatment (5 to 20 times of clinical dosage). Brains of the rats were examined 48 h or 72 h after interventions in a random order. Image processing software was used in the calculation of volume of cerebral infarction. Conventional HE staining was used for observation of brain tissue. Immunohistochemical method was used to determine NF-κB expression. Results Compared with the model group, rats treated with Shenxiong Pill and cyclophosphamide had lower infarct brain volumes (P<0.05). NF-κB positive inflammatory cells were not found in the normal and sham groups. But the MCAO model rats had increased numbers of NF-κB positive inflammatory cells and higher integral optical density of NF-κB over time. Compared with the model group, lower numbers and expression of NF-κB positive inflammatory cells were found in those treated with Shenxiong Pill (P<0.05). Higher dosage of Shenxiong was associated with lower numbers and expression of NF-κB inflammatory cells (P<0.05). Conclusion Shenxiong Pill can reduce pathological damage to brains as a result of cerebral ischemia, possibly through inhibiting the expression and activation of NF-κB.